Although the etiology of rheumatoid arthritis remains obscure, a substantial antibody response occurs at the site of tissue injury. Rheumatoid factor may account for as much as 30% of the locally produced antibody, but the specificity of the remaining antibody is unknown. We plan to use a large panel of mouse monoclonal antibodies to human VH subgroups, cross-reactive idiotypes and isotypes to compare the diversity of antibody producing cells in synovial tissues and blood from patients with rheumatoid arthritis. A marked discrepancy in isotype, idiotype and HV subgroup expression by B lineage cells in blood and synovium would suggest a distinctive local antibody response. We will explore the antigenic specificity of the antibodies produced by clones of B cells rescued from affected synovium. To do this we will utilize EBV-transformation and cell hybridization techniques to immortalize synovial B cells. We will use radioimmunoassays, enzyme-linked immunoabsorbent assays and immunofluorescence to search for antibodies against antigens on immunoglobulins, synovial tissues, lymphocytes and other types of blood cells. The discrete tissue distribution and nature of the antigens detected by locally produced antibodies will be analyzed by immunochemical and immunofluorescence methods. Monoclonal anti-idiotype antibodies will also be made to idiotypic determinants of locally produced antibodies of interesting specificity. These studies of the clones of B cells in the synovium and the antigens with which they react could provide new insight into the pathogenesis of rheumatoid arthritis.